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Background To depict ecthyma gangrenosum (EG) clinical presentation and evolution in a large multicenter pediatric retrospective collection of children with malignancies or bone marrow failure syndromes, to facilitate early diagnosis. Methods EG episodes diagnosed in the period 2009-2019 were identified by a retrospective review of clinical charts at centers belonging to the Italian Pediatric Hematology Oncology Association. Results Thirty-eight cases of EG occurring in children (male/female 16/22; median age 5.2 years) with hematologic malignancy (29), allogeneic stem cell transplantation (2) or relapsed/refractory solid tumor (3) were collected. The involved sites were: perineal region (19), limbs (10), trunk (6), head and the iliac crest (3). Bacteremia was present in 22 patients. Overall, the germs isolated were Pseudomonas aeruginosa (30), Stenotrophomonas maltophilia (3) and Escherichia coli (1); 31% of them were multidrug-resistant. All patients received antibacterial treatment, while surgery was performed in 24 patients (63.1%). Predisposing underlying conditions for EG were severe neutropenia (97.3%), corticosteroid treatment (71%) and iatrogenic diabetes (23.7%). All patients recovered, but EG recurred in 5 patients. Nine patients (24%) showed sequelae (deep scars, with muscle atrophy in 2). Four patients (10.5%) died, 1 due to relapse of EG with Carbapenem-resistant Enterobacteriaceae co-infection and 3 due to the progression of the underlying disease. Conclusions EG requires early recognition and a proper and timely treatment to obtain the recovery and to avoid larger necrotic lesions, eventually evolving in scarring sequelae.

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. Cardiac involvement is common in FD and is responsible for impaired quality of life and premature death. The classic cardiac involvement is a nonobstructive form of hypertrophic cardiomyopathy, usually manifesting as concentric left ventricular hypertrophy, with subsequent arrhythmogenic intramural fibrosis. Treatment of patients with FD should be directed to prevent the disease progression to irreversible organ damage and organ failure. The aim of this review is to describe the current state of knowledge regarding cardiovascular involvement in FD, focusing on clinical and instrumental features, cardiovascular management, and targeted therapy.

Malignant pleural effusion represents a prognostic negative factor on survival conferring stage IV disease. The median of survival is 5 months and a 5-year survival of about 3%. We describe the therapeutic success obtained from different strategies in anaplastic lymphoma kinase (ALK) inhibitors in 2 young women showing malignant pleural effusion secondary to advanced ALK-rearranged lung adenocarcinoma. This report shows that for patients with EGFR mutations in advanced lung adenocarcinoma-associated malignant pleural effusion, complete response to EGFR TKI inhibitor can be observed mostly if pleural effusion and primary lung adenocarcinoma show the same EGFR mutation status.

BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Heart failure (HF) is an important health care issue in children because of its considerable morbidity and mortality. Advanced HF encompasses patients who remained symptomatic despite optimal medical treatment and includes patients who require special management, such as continuous inotropic therapy, mechanical circulatory support, or heart transplantation (HT). HT is the gold standard for children with advanced HF; nonetheless, the number of suitable donors has not increased for decades, leading to prolonged waitlist times and increased mortality rates. Therefore, the role of pediatric mechanic circulatory support has been assessed as an alternative treatment in patients in whom heart transplant could not be performed. The authors discuss the epidemiology, causes, pathophysiology, clinical manifestation, medical treatment, device therapy, and HT in pediatric HF, and a particular emphasis was posed on patients with advanced HF.

Severe hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of haematopoietic cell transplantation (HCT). This multinational, prospective, observational study (NCT03032016), performed by the EBMT, enrolled patients treated with defibrotide from April 2015 to July 2018. This analysis focused on defibrotide-treated patients with VOD/SOS post-HCT. The primary endpoint was incidence of serious adverse events (SAEs) of interest up to 12 months post-HCT in patients with severe VOD/SOS. Overall, 104 defibrotide-treated patients with VOD/SOS post-HCT were enrolled: 62 had severe VOD/SOS and comprised the primary study population, including 36 with multi-organ dysfunction/failure (MOD/MOF). SAEs of interest occurred in 20 of 62 (32%) severe VOD/SOS patients; the most common by category were infection (24%) and bleeding (13%). In patients with severe VOD/SOS, the Kaplan–Meier–estimated Day 100 survival rate was 73% (95% CI: 60%, 82%) with VOD/SOS resolution by Day 100 in 45 of 62 (73%) patients. MOD/MOF resolved in 19 of 36 (53%) patients with MOD/MOF at VOD/SOS diagnosis. Results from this multicentre registry study build on prior defibrotide studies supporting the utility of defibrotide for the treatment of VOD/SOS post-HCT. These results provide additional real-world evidence of the effectiveness and safety of defibrotide in patients with VOD/SOS post-HCT.

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder. The most common cause is a mutation in both alleles of the gene encoding for the low-density lipoprotein (LDL) receptor, although other causative mutations have been identified. Complications of atherosclerotic cardiovascular disease are common in these patients; therefore, reducing the elevated LDL-cholesterol burden is critical in their management. Conventionally, this is achieved by patients initiating lipid-lowering therapy, but this can present challenges in clinical practice. Fortunately, novel therapeutic strategies have enabled promising innovations in HoFH treatment. This review highlights recent and ongoing studies examining new therapeutic options for patients with HoFH.

Background: Peripheral arterial disease (PAD) was reported to increase the risk of new cardiovascular events in patients with acute coronary syndromes (ACS). However, most of the evidence comes from randomized clinical trials. We aimed to assess the impact of PAD on cardiovascular outcome and treatment decisions in ACS patients in a current real-life setting. Methods: START-ANTIPLATELET is a multicenter registry enrolling ACS patient. Baseline clinical characteristics and treatment at discharge were recorded and follow-up was repeated at 6-months and 1-year. PAD was defined as intermittent claudication and/or previous revascularization. Results: Among 1442 patients enrolled, 103 (7.1%) had PAD. PAD patients were older (71.8 ± 10.6vs66.2 ± 12.6 yrs., p < 0.0001), more frequently hypertensive (90.3vs68.6%, p< 0.0001), hypercholesterolemic (66vs52%, p= 0.037), diabetic (51.5vs24%, p= 0.0001), obese (28.2vs19.3%, p= 0.029) and with previous TIA (7.8vs2.8%, p= 0.005) or stroke (11.7vs3.1%, p< 0.0001). Clinical presentation and acute treatment were similar in non-PAD and PAD patients, but the latter were discharged significantly less frequently on dual antiplatelet therapy (DAPT) (68.9vs85%, p= 0.005). After a median follow-up time of 11.1 months, major cardio/cerebrovascular event-free survival [MACCE, including cardiovascular death, MI, TIA and stroke, target-vessel revascularization (TVR) and major arterial ischemic events] was significantly shorter (9.0vs11.2 months, p= 0.02; HR 3.2, 2.4–8.4) in PAD patients and net adverse cardiovascular events (NACE = MACCE plus major hemorrhages) were significantly more frequent (19.1%vs10.5%, p = 0.049). Conclusions: PAD identifies a subgroup of ACS patients at significantly increased cardiovascular risk, but these patients tend to be undertreated. Patients admitted for ACS should be screened for PAD and optimal medical therapy at discharge should be implemented.

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Italy (n = 30) and the other with LA in France (n = 29). Results The two cohorts differed significantly for genotype (p = 0.004), baseline lipid profile (p padj = 0.004). Yearly on-treatment LDL-C padj = 0.002). A trend towards fewer total cardiovascular events was observed in the Lomitapide than in the LA cohort. Conclusions In comparison with LA, lomitapide appears to provide a better control of LDL-C in HoFH. Further studies are needed to confirm this data and establish whether this translates into a reduction of cardiovascular risk.

Adenosine deaminase 2 deficiency (DADA2) is a rare inherited disorder that is caused by autosomal recessive mutations in the ADA2 gene. Clinical manifestations include early-onset lacunar strokes, vasculitis/vasculopathy, systemic inflammation, immunodeficiency, and hematologic defects. Anti–tumor necrosis factor therapy reduces strokes and systemic inflammation. Allogeneic hematopoietic stem/progenitor cell (HSPC) transplantation can ameliorate most disease manifestations, but patients are at risk for complications. Autologous HSPC gene therapy may be an alternative curative option for patients with DADA2. We designed a lentiviral vector encoding ADA2 (LV-ADA2) to genetically correct HSPCs. Lentiviral transduction allowed efficient delivery of the functional ADA2 enzyme into HSPCs from healthy donors. Supranormal ADA2 expression in human and mouse HSPCs did not affect their multipotency and engraftment potential in vivo. The LV-ADA2 induced stable ADA2 expression and corrected the enzymatic defect in HSPCs derived from DADA2 patients. Patients’ HSPCs re-expressing ADA2 retained their potential to differentiate into erythroid and myeloid cells. Delivery of ADA2 enzymatic activity in patients’ macrophages led to a complete rescue of the exaggerated inflammatory cytokine production. Our data indicate that HSPCs ectopically expressing ADA2 retain their multipotent differentiation ability, leading to functional correction of macrophage defects. Altogether, these findings support the implementation of HSPC gene therapy for DADA2.

Background Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up. Methods Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up. Results Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms. Conclusion Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors., Graphical abstract Unlabelled Image

An ultrasonic heading measurement method, working under magnetic interference prohibitive for magnetometers, was prototyped, validated, and metrologically characterized. Two capacitive ultrasonic transducers convert the mechanical rotation in two correspondingly time-delayed electrical sine waves. Then, the time delay is estimated using the standard tree parameter sine-fitting algorithm. The prototyped goniometer achieves the same repeatability level (

Lipoprotein(a) [Lp(a)] is an established cardiovascular risk factor, and growing evidence indicates its causal association with atherosclerotic disease because of the proatherogenic low-density lipoprotein (LDL)-like properties and the prothrombotic plasminogen-like activity of apolipoprotein(a) [apo(a)]. As genetics significantly influences its plasma concentration, Lp(a) is considered an inherited risk factor of atherosclerotic cardiovascular disease (ASCVD), especially in young individuals. Moreover, it has been suggested that elevated Lp(a) may significantly contribute to residual cardiovascular risk in patients with coronary artery disease and optimal LDL-C levels. Nonetheless, the fascinating hypothesis that lowering Lp(a) could reduce the risk of cardiovascular events - in primary or secondary prevention - still needs to be demonstrated by randomized clinical trials. To date, no specific Lp(a)-lowering agent has been approved for reducing the lipoprotein levels, and current lipid-lowering drugs have limited effects. In the future, emerging therapies targeting Lp(a) may offer the possibility to further investigate the relation between Lp(a) levels and cardiovascular outcomes in randomized controlled trials, ultimately leading to a new era in cardiovascular prevention. In this review, we aim to provide an updated overview of current evidence on Lp(a) as well as currently investigated therapeutic strategies that specifically address the reduction of the lipoprotein.

Background: Both the prevalence of sinonasal inverted papilloma (IP) and the causal association with alpha-human papillomaviruses (alpha-HPVs) are controversial. In this study we aimed to determine HPV status in histologically selected, microdissected, formalin-fixed, and paraffin-embedded tissue samples of IP. Methods: HPV status was assessed retrospectively by polymerase chain reaction (PCR)-bead‒based multiplex genotyping on tissue samples of patients diagnosed with IP and consecutively treated with endoscopic resection. Forty-one HPV genotypes were considered, distinguishing between high risk and low risk. HPV status was correlated with demographics and clinical variables. Sixty sinonasal IP tissue samples were initially considered. After exclusion of 5 cases due to insufficient quality/quantity of the samples, 55 patients were included for analysis. Results: HPV-DNA sequences were identified in 34 of 55 (61.8%) IPs, with a higher prevalence of high-risk than low-risk HPV genotypes (19 [55.9%] and 15 cases [44.1%], respectively). HPV16 strongly prevailed among the high-risk HPV cases (84.2%), and HPV54 prevailed among the low-risk HPV cases (53.3%). IPs with origin within the maxillary sinus were significantly associated with high-risk HPV (p = 0.019). No significant associations emerged between HPV status and demographics or clinical variables. Conclusion: In a series of 55 IP tissue samples, HPV-DNA sequences were identified in 61.8% of cases, which differs from the data of previous investigations. Further case-control studies are advocated to confirm this prevalence in the Italian population addressed, and also to clarify any pathogenic involvement of HPV in the natural history of IPs.

Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.

Introduction: Colorectal cancer is the second leading cause of cancer-related death in the US; complete surgical resection is the only curative treatment for non-metastatic colorectal cancer (NMCC). Postoperative ileus (POI) frequently increases patient morbidity and healthcare costs. Enhanced recovery after surgery (ERAS) protocol is the standard of care in most institutions and has been shown to reduce postoperative complications, but there is no a completely effective treatment for this condition. Studies suggest that electroacupuncture (EA) can improve gastrointestinal tract function after surgery. Objective: We aim to determine if including EA in the standard treatment of POI decreases the time to the first defecation, enhancing the return of normal bowel function after colon resection for NMCC. Methods: We propose a phase II, single-center, randomized, triple-blinded, sham-controlled trial with two parallel arms and a 1:1 allocation ratio. Patients 40-80 years of age diagnosed with NMCC scheduled to undergo laparoscopic surgery for colon cancer resection will be included. The arms will be EA + standard treatment and sham EA + standard treatment. The standard treatment will follow the ERAS protocol. Discussion: This will be the first randomized clinical trial to evaluate the impact of using EA along with the ERAS protocol for POI. This intervention may reduce patient morbidity and improve healthcare costs associated with the disease.

Hakarl is a fermented fish traditionally produced in Iceland. In the present study, no scientific research has so far discussed the implication of histamine in this food. The first quantification o...

Paediatric patients with cancer and those undergoing haematopoietic cell transplantation are at high risk of bacterial infections. The 8th European Conference on Infections in Leukaemia (ECIL-8) convened a Paediatric Group to review the literature and to formulate recommendations for the use of antibiotics according to the European Society of Clinical Microbiology and Infectious Diseases grading system. The evaluation of antibacterial prophylaxis included mortality, bloodstream infection, febrile neutropenia, emergence of resistance, and adverse effects as endpoints. Initial antibacterial therapy and antibiotic de-escalation or discontinuation focused on patients with a clinically stable condition and without previous infection or colonisation by resistant bacteria, and on patients with a clinically unstable condition or with previous infection or colonisation by resistant bacteria. The final considerations and recommendations of the ECIL-8 Paediatric Group on antibacterial prophylaxis, initial therapy, and de-escalation strategies are summarised in this Policy Review.

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources.

The present manuscript aims to review the history, recent advances, evidence, and challenges of artificial intelligence (AI) in colonoscopy. Although it is mainly focused on polyp detection and characterization, it also considers other potential applications (i.e., inflammatory bowel disease) and future perspectives. Some of the most recent algorithms show promising results that are similar to human expert performance. The integration of AI in routine clinical practice will be challenging, with significant issues to overcome (i.e., regulatory, reimbursement). Medico-legal issues will also need to be addressed. With the exception of an AI system that is already available in selected countries (GI Genius; Medtronic, Minneapolis, MN, USA), the majority of the technology is still in its infancy and has not yet been proven to reach a sufficient diagnostic performance to be adopted in the clinical practice. However, larger players will enter the arena of AI in the next few months.

The risk of ischemic events carried by different clusters of type 2 diabetes mellitus (DM) in the setting of secondary prevention is not definite and the association between DM and bleeding complications is controversial. We explored these issues in the START-ANTIPLATELET, a multicenter Italian registry including acute coronary syndrome (ACS) patients. Study outcome was 1-year incidence of the net composite endpoint including major adverse cardiovascular events (MACE) or any bleeding and its individual components across different DM strata (no DM, DM with or without insulin). Out of 951 patients, 20.0% had diabetes not on insulin and 2.5% had diabetes on insulin. The rate of the net composite endpoint was highest in patients receiving insulin (39.4 per 100 person-years vs 11.7 in diabetic patients not on insulin vs 14.0 in those without DM; p = 0.007). In DM, the higher risk of MACE was regardless of insulin use (p = 0.36). Conversely, the increase in bleeding complications was limited to patients on insulin (Hazard Ratio 2.31, 95% CI 0.93-5.71 vs no DM; p = 0.0105 across DM strata). On top of aspirin, the rates of the net composite endpoint were similar with ticagrelor/prasugrel or clopidogrel irrespective of DM status (p for interaction 0.63). In conclusion, in ACS patients, type 2 DM enhances the risk of MACE regardless of the DM cluster, whereas the propensity to bleeding related to DM seems confined to insulin-treated patients.

Laboratory medicine, along with genetic investigations in sports medicine, is taking on an increasingly important role in monitoring athletes’ health conditions. Acute or intense exercise can result in metabolic imbalances, muscle injuries or reveal cardiovascular disorders. This study aimed to monitor the health status of a basketball player with an integrated approach, including biochemical and genetic investigations and advanced imaging techniques, to shed light on the causes of recurrent syncope he experienced during exercise. Biochemical analyses showed that the athlete had abnormal iron, ferritin and bilirubin levels. Coronary Computed Tomographic Angiography highlighted the presence of an intramyocardial bridge, suggesting this may be the cause of the observed syncopes. The athlete was excluded from competitive activity. In order to understand if this cardiac malformation could be caused by an inherited genetic condition, both array-CGH and whole exome sequencing were performed. Array-CGH showed two intronic deletions involving MACROD2 and COMMD10 genes, which could be related to a congenital heart defect; whole exome sequencing highlighted the genotype compatible with Gilbert syndrome. However, no clear pathogenic mutations related to the patient’s cardiological phenotype were detected, even after applying machine learning methods. This case report highlights the importance and the need to provide exhaustive personalized diagnostic work up for the athletes in order to cover the cause of their malaise and for safeguarding their health. This multidisciplinary approach can be useful to create ad personam training and treatments, thus avoiding the appearance of diseases and injuries which, if underestimated, can become irreversible disorders and sometimes can result in the death of the athlete.

Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding Associazione Lorenzo Risolo.

Patients with bicuspid aortic valve (BAV) have an increased risk of aortic dilation and aortic dissection or rupture. The impact of physical training on the natural course of aortopathy in BAV patients remains unclear. The aim of this study was to evaluate the impact of regular physical activity on aortic diameters in a consecutive cohort of paediatric patients with BAV. Consecutive paediatric BAV patients were evaluated and categorized into two groups: physically active and sedentary subjects. Only the subjects with a complete 2-year follow-up were included in the study. To evaluate the potential impact of physical activity on aortic size, aortic diameters were measured at the sinus of Valsalva and mid-ascending aorta using echocardiography. We defined aortic diameter progression the increase of aortic diameter ≥ 10% from baseline. Among 90 BAV patients (11.5 ± 3.4 years of age, 77% males), 53 (59%) were physically active subjects. Compared to sedentary, physically active subjects were not significantly more likely to have > 10% increase in sinus of Valsalva (13% vs. 8%, p-value = 0.45) or mid-ascending aorta diameter (9% vs. 13%, p-value = 0.55) at 2 years follow-up, both in subjects with sinus of Valsalva diameter progression (3.7 ± 1.0 mm vs. 3.5 ± 0.8 mm, p-value = 0.67) and in those with ascending aorta diameter progression (3.0 ± 0.8 mm vs. 3.2 ± 1.3 mm, p-value = 0.83). In our paediatric cohort of BAV patients, the prevalence and the degree of aortic diameter progression was not significantly different between physically active and sedentary subjects, suggesting that aortic dilation is unrelated to regular physical activity over a 2-year period.

Aim To analyze the prevalence and clinical implications of the eligibility criteria for prolonged dual antithrombotic therapy with ticagrelor 60 mg twice daily and/or rivaroxaban 2.5 mg twice daily in a contemporary real-world ACS registry. Methods Patients from the START-ANTIPLATELET registry ( NCT02219984 ) were stratified according to the eligibility criteria of the PEGASUS and COMPASS studies to investigate the proportion of patients eligible for prolonged dual antithrombotic therapy at discharge and after 1-year of DAPT. Net adverse clinical events (NACE), defined as all-cause death, myocardial infarction, stroke, and major bleeding, at 1 year were also evaluated and compared among groups. Results 1844 were considered for the analysis at baseline. Out of 849 event-free patients continually receiving dual antiplatelet therapy for at least 1 year, 577 (68%) and 583 (68.7%) met at least one eligibility criterion for ticagrelor and rivaroxaban, respectively. In the PEGASUS-like patients, age was the most common criterion (71% of cases). The presence ≥2 cardiovascular risk factors was the most common eligibility criterion in the COMPASS-like patients (80.8%). At 1-year follow-up, 211 (11.4%) and 119 (6.5%) patients experienced NACE and MACE, respectively. The incidence of NACEs was higher in the PEGASUS-only group (15.4% vs. 8.4%; p = 0.008) and numerically higher in the COMPASS-only group (10.9% vs. 8.4%; p = 0.299). Conclusions In a contemporary real-world ACS cohort, approximately two-thirds of patients that complete 1-year DAPT met the eligibility criteria for ticagrelor 60 mg twice daily or rivaroxaban 2.5 mg twice daily, showing a higher risk of NACEs.

Background: Previous studies have shown that children and adolescents with COVID-19 generally have mild disease. Children and adolescents with cancer, however, can have severe disease when infected with respiratory viruses. In this study, we aimed to understand the clinical course and outcomes of SARS-CoV-2 infection in children and adolescents with cancer. Methods: We did a cohort study with data from 131 institutions in 45 countries. We created the Global Registry of COVID-19 in Childhood Cancer to capture de-identified data pertaining to laboratory-confirmed SARS-CoV-2 infections in children and adolescents (

Contemporary evidence supports device-based transcatheter interventions for the management of patients with structural heart disease. These procedures, which include aortic valve implantation, mitral or tricuspid valve repair/implantation, left atrial appendage occlusion, and patent foramen ovale closure, profoundly differ with respect to clinical indications and procedural aspects. Yet, patients undergoing transcatheter cardiac interventions require antithrombotic therapy before, during, or after the procedure to prevent thromboembolic events. However, these therapies are associated with an increased risk of bleeding complications. To date, challenges and controversies exist regarding balancing the risk of thrombotic and bleeding complications in these patients such that the optimal antithrombotic regimens to adopt in each specific procedure is still unclear. In this review, we summarize current evidence on antithrombotic therapies for device-based transcatheter interventions targeting structural heart disease and emphasize the importance of a tailored approach in these patients.

The first studies on Staphylococcus aureus (SA) infections in athletes were conducted in the 1980s, and examined athletes that perform in close physical contact, with particular attention to damaged or infected skin. Recent studies have used molecular epidemiology to shed light on the transmission of SA in professional athletes. These studies have shown that contact between athletes is prolonged and constant, and that these factors influence the appearance of infections caused by SA. These results support the need to use sanitary measures designed to prevent the appearance of SA infections. The factors triggering the establishment of SA within professional sports groups are the nasal colonization of SA, contact between athletes and sweating. Hence, there is a need to use the most modern molecular typing methods to evaluate the appearance of cutaneous SA disease. This review aims to summarize both the current SA infections known in athletes and the diagnostic methods employed for recognition, pointing to possible preventive strategies and the factors that can act as a springboard for the appearance of SA and subsequent transmission between athletes.

Evidence suggests a close connection between Nonalcoholic Fatty Liver Disease (NAFLD) and increased cardiovascular (CV) risk. Several cross-sectional studies report that NAFLD is related to preclinical atherosclerotic damage, and to coronary, cerebral and peripheral vascular events. Similar results have been showed by prospective studies and also by meta-analyzes on observational studies. The pathophysiological mechanisms of NAFLD are related to insulin resistance, which causes a dysfunction in adipokine production, especially adiponectin, from adipose tissue. A proinflammatory state and an increase in oxidative stress, due to increased reacting oxygen species (ROS) formation with consequent oxidation of free fatty acids and increased de novo lipogenesis with accumulation of triglycerides, are observed. These mechanisms may have an impact on atherosclerotic plaque formation and progression, and they can lead to increased cardiovascular risk in subjects with NAFLD. This review extensively discusses and comments current and developing NAFLD therapies and their possible impact on cardiovascular outcome.

Rheumatic mitral stenosis is still a pathological condition that affects young patients and is an important cause of mortality. 2017-European Guidelines for the management of valvular heart disease suggest a percutaneous approach with a mitral commissurotomy for the treatment of symptomatic pregnant women. Mitral commissurotomy procedure involves radiation exposure that is incompatible with the pregnancy condition. In our case, we present percutaneous mitral commissurotomy (PMC) to a 28-week pregnant woman with a low-radiation dose and the use of transesophageal echocardiography. The woman presented with a mitral transvalvular mean gradient of 21.6mmHg and with symptoms non-responsive to medical treatment. PMC was driven by a transesophageal echocardiographic probe. This case demonstrates the feasibility and safety of PMC in a pregnant woman with severe rheumatic mitral stenosis.

Background Patients with prior colon cancer have increased risk of metachronous colorectal neoplasms; therefore, endoscopic surveillance is indicated. Current recommendations are not risk-stratified. We investigated predictive factors for colorectal neoplasms to build a model to spare colonoscopies for low-risk patients. Methods This was a multicenter, retrospective study including patients who underwent surgery for colon cancer in 2001 – 2008 (derivation cohort) and 2009 – 2013 (validation cohort). A predictive model for neoplasm occurrence at second surveillance colonoscopy was developed and validated. Results 421 and 203 patients were included in derivation and validation cohort, respectively. At second surveillance colonoscopy, 112 (26.6 %) and 55 (27.1 %) patients had metachronous neoplasms in derivation and validation groups; three cancers were detected in the latter. History of left-sided colon cancer (OR 1.64, 95 %CI 1.02 – 2.64), ≥ 1 advanced adenoma at index colonoscopy (OR 1.90, 95 %CI 1.05 – 3.43), and ≥ 1 adenoma at first surveillance colonoscopy (OR 2.06, 95 %CI 1.29 – 3.27) were independently predictive of metachronous colorectal neoplasms at second surveillance colonoscopy. For patients without such risk factors, diagnostic accuracy parameters were: 89.3 % (95 %CI 82.0 %-94.3 %) and 78.2 % (95 %CI 65.0 %-88.2 %) sensitivity, and 28.5 % (95 %CI 23.5 %-33.9 %) and 33.8 % (95 %CI 26.2 %-42.0 %) specificity in derivation and validation group, respectively. No cancer would be missed. Conclusions Patients with prior left-sided colon cancer or ≥ 1 advanced adenoma at index colonoscopy or ≥ 1 adenoma at first surveillance colonoscopy had a significantly higher risk of neoplasms at second surveillance colonoscopy; patients without such factors had much lower risk and could safely skip the second surveillance colonoscopy. A prospective, multicenter validation study is needed.

Information on incidence, and factors associated with mortality is a prerequisite to improve outcome after hematopoietic stem cell transplantation (HSCT). Therefore, 55′668 deaths in 114′491 patients with HSCT (83.7% allogeneic) for leukemia were investigated in a landmark analysis for causes of death at day 30 (very early), day 100 (early), at 1 year (intermediate) and at 5 years (late). Mortality from all causes decreased from cohort 1 (1980–2001) to cohort 2 (2002–2015) in all post-transplant phases after autologous HSCT. After allogeneic HSCT, mortality from infections, GVHD, and toxicity decreased up to 1 year, increased at 5 years; deaths from relapse increased in all post-transplant phases. Infections of unknown origin were the main cause of infectious deaths. Lethal bacterial and fungal infections decreased from cohort 1 to cohort 2, not unknown or mixed infections. Infectious deaths were associated with patient-, disease-, donor type, stem cell source, center, and country- related factors. Their impact varied over the post-transplant phases. Transplant centres have successfully managed to reduce death after HSCT in the early and intermediate post-transplant phases, and have identified risk factors. Late post-transplant care could be improved by focus on groups at risk and better identification of infections of “unknown origin”., The study was funded by the European Group for Blood and Marrow Transplantation EBMT

Item does not contain fulltext We assessed the incidence and outcome of early candidemia after hematopoietic stem cell transplant (HSCT). The analysis included all first HSCTs performed from 2000 to 2015 in adult and pediatric patients with a non-leukemic disease and recorded in the EBMT registry. Overall survival (OS), non-relapse mortality (NRM), and relapse mortality (RM) were evaluated. Candidemia was diagnosed in 420 of 49,852 patients at a median time of 17 days post HSCT (range 0-100), the cumulative incidence being 0.85%. In 65.5% of episodes, candidemia occurred by day 30 after HSCT. The mortality rate by day 7 was 6.2%, whereas 100-day NRM was higher (HR 3.47, p

Objectives: We present here data on Gram-negative rods bacteremia (GNRB) rates, risk factors and associated mortality. Methods: Data on GNRB episodes were prospectively collected in 65 allo-/67 auto-HSCT centers in 24 countries (Europe, Asia, Australia). In patients with and without GNRB, we compared: demography, underlying disease, HSCT-related data, center' fluoroquinolone prophylaxis (FQP) policy and accreditation status, and involvement of infection control team (ICT). Results: The GNRB cumulative incidence among 2818 allo-HSCT was: pre-engraftment (pre-eng-alloHSCT), 8.4 (95% CI 7-9%), post-engraftment (post-eng-allo-HSCT), 5.8% (95%CI: 5-7%); among 3152 auto-HSCT, pre-eng-auto-HSCT, 6.6% (95%CI: 6-7%), post-eng-auto-HSCT, 0.7% (95%CI: 0.4-1.1%). GNRB, especially MDR, was associated with increased mortality. Multivariate analysis revealed the following GNRB risk factors: (a) pre-eng-allo-HSCT: south-eastern Europe center location, underlying diseases not at complete remission, and cord blood source; (b) post-eng-allo-HSCT: center location not in northwestern Europe; underlying non-malignant disease, not providing FQP and never accredited. (c) pre-eng-auto-HSCT: older age, autoimmune and malignant (vs. plasma cell) disease, and ICT absence. Conclusions: Benefit of FQP should be explored in prospective studies. Increased GNRB risk in auto-HSCT patients transplanted for autoimmune diseases is worrying. Infection control and being accredited are possibly protective against bacteremia. GNRB are associated with increased mortality. (C) 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

A Spigelian hernia is a rare hernia, making up approximately 0.1% of all abdominal wall hernias. This hernia goes through a defect in the Spigelian fascia which is the part of the transversus abdominis aponeurosis lateral to the rectus muscle, often at the level of the arcuate line, where the fascia is widest and weakest. Clinical diagnosis is difficult in patients without obvious abdominal mass but imaging can be a valuable adjunct in diagnosis. We report the case of a 64-year-old male who presented to our hospital with small bowel obstruction secondary to an incarcerated Spigelian hernia who was pre-operatively diagnosed with ultrasound and computed tomography. At ultrasound and computed tomography a closed loop obstruction in a Spigelian Hernia was detected, resembling on both imaging modalities a "bulb-like" appearance.

In hematopoietic cell transplantation (HCT) patients, BK polyomavirus (BKPyV) infection results in significant morbidity mainly due to hemorrhagic cystitis (HC). Despite increased knowledge acquired over recent decades, no treatment has shown effectiveness in the management of organ damage in HCT allografts. This review summarizes the current knowledge on BKPyV, from the virus constitution to the pathophysiology and immune-related mechanisms. We next focus on BKPyV-induced HC in HCT to discuss the benefit of monitoring BKPyV viruria and viremia in the management of patients. At last, we review currently used therapeutics, along with future promising therapies to propose clinical and practical guidelines and further interesting research areas.

BackgroundIn patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders.ObjectiveWe analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival (OS); relapse-free survival (RFS); relapse incidence (RI); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT.Patients and MethodsA total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study.ResultsDemographics: The median age of recipient was 17.7 years (range: 0–77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R−/D−, R−/D+, R+/D−, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD.ConclusionsAllo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.

SIGNIFICANCE Peripapillary retinoschisis is associated with primary and secondary glaucoma. It is important that clinicians are familiar with the presentation and management of peripapillary retinoschisis to understand its effects on the patient's glaucoma and to avoid unnecessary referral when the macula is not involved. PURPOSE We present a case of peripapillary retinoschisis found incidentally on routine optical coherence tomographic (OCT) surveillance of primary open-angle glaucoma. CASE REPORT A 70-year-old man presented for his annual diabetic eye examination. Surveillance with OCT revealed a splitting of the inner peripapillary retina corresponding to a previously noted notch in the right optic nerve. Further imaging of the right eye using enhanced depth imaging OCT revealed a defect in the lamina cribrosa that may have contributed to the formation and persistence of peripapillary retinoschisis. Retinal nerve fiber layer analysis showed a 5-year history of progressive temporal and inferotemporal thickening in the right eye. The patient was managed conservatively with instruction on regular Amsler grid testing. CONCLUSIONS As seen in this case, peripapillary retinoschisis typically alters retinal nerve fiber layer thickness on OCT and can be mistakenly attributed to glaucomatous change. Glaucoma-associated peripapillary retinoschisis is usually not vision threatening and can be managed conservatively; in rare cases of progression to macular involvement, patients should be referred to a retina specialist.

Idiopathic aplastic anemia is a rare and life-threatening disorder, and hematopoietic stem cell transplantation (HSCT) from a matched sibling donor (MSD) is the standard treatment strategy for young patients. Alternative donor transplantation (ADT) from a matched unrelated donor or an HLA haploidentical donor is not commonly used in the frontline setting. This systematic review/meta-analysis was conducted to compare ADT as an upfront, rather than delayed, treatment strategy in the absence of an MSD to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). We searched PubMed/MEDLINE and Embase (1998 to 2019) for studies that compared the outcomes of ADT with IST as upfront therapy in patients with SAA. We included studies with 5 patients or more in each arm. Studies that included patients with inherited forms of bone marrow failure syndromes were excluded. The primary outcome was the 5-year overall survival (OS) rate. Five studies met the inclusion criteria and were included in this meta-analysis. The pooled 5-year odds ratio (OR) for OS was statistically significant at 0.44 (95% confidence interval [CI], 0.23 to 0.85) in favor of upfront ADT. In addition, survival was compared between upfront ADT versus salvage ADT in 6 studies. The pooled 5-year OR for OS was statistically significant at 0.31 (95% CI, 0.15 to 0.64) in favor of upfront ADT. Although this analysis has some limitations, including the retrospective nature of the included studies, the lack of ethnic diversity, the predominantly pediatric population, and the relatively suboptimal IST regimen used in some of the studies, it indicates that upfront ADT is a potential alternative treatment option in young and pediatric SAA patients who lack an HLA identical sibling donor, particularly when optimal IST is not available. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Terapia profiláctica antibiótica; Niños; Vacunación Teràpia profilàctica antibiòtica; Nens; Vacunació Antibiotic prophylactic therapy; Children; Vaccination Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.

Purpose Deficiency of adenosine deaminase 2 (DADA2) is an inherited inborn error of immunity, characterized by autoinflammation (recurrent fever), vasculopathy (livedo racemosa, polyarteritis nodosa, lacunar ischemic strokes, and intracranial hemorrhages), immunodeficiency, lymphoproliferation, immune cytopenias, and bone marrow failure (BMF). Tumor necrosis factor (TNF-α) blockade is the treatment of choice for the vasculopathy, but often fails to reverse refractory cytopenia. We aimed to study the outcome of hematopoietic cell transplantation (HCT) in patients with DADA2. Methods We conducted a retrospective study on the outcome of HCT in patients with DADA2. The primary outcome was overall survival (OS). Results Thirty DADA2 patients from 12 countries received a total of 38 HCTs. The indications for HCT were BMF, immune cytopenia, malignancy, or immunodeficiency. Median age at HCT was 9 years (range: 2–28 years). The conditioning regimens for the final transplants were myeloablative (n = 20), reduced intensity (n = 8), or non-myeloablative (n = 2). Donors were HLA-matched related (n = 4), HLA-matched unrelated (n = 16), HLA-haploidentical (n = 2), or HLA-mismatched unrelated (n = 8). After a median follow-up of 2 years (range: 0.5–16 years), 2-year OS was 97%, and 2-year GvHD-free relapse-free survival was 73%. The hematological and immunological phenotypes resolved, and there were no new vascular events. Plasma ADA2 enzyme activity normalized in 16/17 patients tested. Six patients required more than one HCT. Conclusion HCT was an effective treatment for DADA2, successfully reversing the refractory cytopenia, as well as the vasculopathy and immunodeficiency. Clinical Implications HCT is a definitive cure for DADA2 with > 95% survival.

Malignant central airway obstruction is a life-threatening condition that often causes respiratory failure. In many cases, treatment of tumor in rigid bronchoscopy must be performed urgently, soothing respiratory symptoms and improving patient quality of life, in many cases reducing time to and allowing application of oncologic therapies. Immuno-oncologic therapies target the immune system selectively and are therefore much less toxic than standard chemotherapies, sometimes leading to outstanding results in advanced cancers for which there were no effective treatments until a few years ago. This report shows the effect of the joint application of rigid bronchoscopy and targeted immunotherapy in an emergency scenario, resulting in an unexpected extraordinary therapeutic success.

A hyperglycemic state, also in non-diabetic subjects, may be associated with acute coronary syndrome (ACS). Aim of this review is to describe the pathophysiologic association between ACS and hyperglycemic state, the protective mechanisms of a tight glycaemic control in ACS on CV outcomes, and the supporting clinical evidence. Several mechanisms may be responsible of a poor CV outcome in subjects with hyperglycemia during ACS. Endothelial NAPDH oxidase-2 (NOX2) activation in response to high glucose alters the balance between Raf/MAPK-dependent vasoconstriction and PI3K/Akt-dependent vasodilation in favour of constriction. Hyperglycaemia induces an overproduction of superoxide by the mitochondrial electron transport chain through different molecular mechanisms. Moreover, hyperglycaemia increases the size of the infarct by causing myocardial cell death through apoptosis and reducing the collateral blood flow. High FFA concentrations lead to toxicity mechanisms in acutely ischemic myocardium. On the other hand, a tight glycaemic control in ACS exerts a cardioprotective action by anti-inflammatory and anti-apoptotic mechanisms, anti-oxidative stress, endothelium protection, FFA reduction, anti-glucotoxic effect, IR and cardiac fuel metabolisms improvement, heart stem cells protection and reduced activation of adrenergic system. Unfortunately, the clinical studies supporting the above pathophysiological background are few and sometimes controversial, more likely due the risk of hypoglycemia linked to the insulin therapy generally used during ACS. Intriguingly, GLP-1 RA and SGLT2i, demonstrated highly effective in the cardiovascular prevention in high-risk subjects without the risk of hypoglycemia, might keep this cardioprotective effect even in acute conditions such as ASC.

Objective Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of survivors of hematological malignancies and/or hematopoietic stem cell transplantation (HSCT) and assessing the relationship between cyclophosphamide equivalent dose (CED) and anti-Müllerian hormone (AMH). Design and methods Gonadal health was clinically and biochemically assessed in 124 post-menarchal survivors who underwent treatment for pediatric hematological malignancies and/or HSCT between 1992 and 2019. Results Overt 'premature ovarian insufficiency' (POI) was detected in 72.1 and 3.7% of transplanted and non-transplanted patients, respectively; milder 'diminished ovarian reserve' (DOR) in 16.3 and 22.2%. In non-transplanted patients, increasing CED values were associated with lower AMH-SDS (P = 0.04), with the threshold of 7200 g/m2 being the best discriminator between DOR/POI and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 g/m2. In addition, age at diagnosis ≥10 years played a detrimental role on ovarian reserve (P = 0.003). In the HSCT group, irradiation was associated with a statistically significant reduction in AMH-SDS (P = 0.04). Conclusions In non-transplanted patients, CED ≥ 7200 mg/m2 was associated with a DOR, while younger age at diagnosis played a protective role on ovarian reserve. As a result of the data collected, we propose a systematic algorithm to assess iatrogenic gonadal impairment in young female patients exposed to chemo-radiotherapy in childhood for hematological disorders.

Prophylaxis of Pneumocystis jiroveci pneumonia (PJP) with trimethoprim/sulfamethoxazole is a standard of care for children with hematologic malignancies, while its use in solid tumor patients is still debated. A retrospective study focusing on the use of PJP prophylaxis in patients with solid tumors was performed among 16 AIEOP centers: 1046/2863 patients did not receive prophylaxis and no cases of PJP were reported.

Introduction: The radial artery is currently the most widely used access site for PCI procedures both acute and stable patient settings. Thanks to advantages in pharmacological therapy as well as in interventional devices, the rate of ischemic complications following PCI has significantly decreased. Nevertheless, this has been counterbalanced by an increased risk of periprocedural and late bleeding event, that can occur both at access and non-access sites. Choice of access site for PCI is of paramount importance to reduce the risk of access-related bleeding events. Areas covered: The aim of this review is to provide an overview of the actual available evidence comparing the transradial versus transfemoral approach to reduce hemorrhagic events. The most robust evidence comes from large randomized trials, partly also from observational registries, which compared the transradial and transfemoral approach. Expert opinion: Results show that radial access has proved to be decisive in reducing the incidence of hemorrhagic events. Furthermore, it showed a significant reduction in mortality and AKI compared to transfemoral access. However, increased experience in the use of the radial approach has led to less practice in the use of the femoral approach, which may be useful in cases of emergency, complications or inability to use the radial artery.